In this project, nervous system disease associated with human herpesvirus infections are examined. Agents include neurotropic herpes simplex virus types 1 and 2 (HSV-1,-2) and varicella zoster virus (VZV), as well as other human herpesviruses known or suspected to infect the nervous system (cytomegalovirus [CMV], Epstein-Barr virus [EBV], and human herpesvirus types 6 and 7 [HHV-6,-7]). For neurotropic herpesviruses, experimental models are used to examine mechanisms underlying production of neural lesions. Problems of particular interest include: the role of infection with HSV, VZV and other herpes viruses in the production of CNS and PNS disease, including (a) acute encephalitis, (b) infection during nervous development, (c) chronic demyelination, and (d) mechanisms of CNS arteritis and stroke induced by neurotropic herpesviruses. During FY 1994, experiments to localize herpesvirus DNA sequences in tissue sections from experimentally infected animals and human autopsy tissues using an in situ polymerase chain reaction (ISPCR) method were continued. A study to identify the cell type containing HSV DNA in the mouse trigeminal root entry zone during acute infection and post-acute period was completed. By ISPCR, HSV DNA sequence-containing nuclei were associated with GFAP-positive process by immunohistochemistry. This colocalization study shows that astrocytes can harbor HSV DNA long-term, and is evidence for persistent or latent HSV infection in a new cell type. Work on identifying herpesvirus sequences in human autopsy tissues was extended to the study of arterial disease with and without association with VZV infection.